BACKGROUND: Mutations in LRRK2 (leucine-rich repeat kinase 2) are a common cause of familial Parkinson's disease. However, the mechanisms through which LRRK2 mutations contribute to neurodegeneration are poorly understood. OBJECTIVE: We investigated the effects of WT, G2019S (GS), R1441C (RC) and kinase dead LRRK2 across multiple different cellular compartments in order to gain insight into the breadth of LRRK2 effects on cellular function. METHODS: Nematodes expressing lgg-1::RFP, hsp1::GFP, hsp4::GFP and hsp6::GFP were crossed to nematode lines expressing WT, GS, RC or kinase dead LRRK2. RESULTS: We observed that GS and RC LRRK2 inhibited autophagy, while WT, GS and RC LRRK2 increased the response of the mitochondrial hsp6 reporter to stress. The response of the hsp reporters under basal conditions was more nuanced. CONCLUSION: These results support a putative role of LRRK2 in the autophagic and mitochondrial systems.
BACKGROUND: Mutations in LRRK2 (leucine-rich repeat kinase 2) are a common cause of familial Parkinson's disease. However, the mechanisms through which LRRK2 mutations contribute to neurodegeneration are poorly understood. OBJECTIVE: We investigated the effects of WT, G2019S (GS), R1441C (RC) and kinase dead LRRK2 across multiple different cellular compartments in order to gain insight into the breadth of LRRK2 effects on cellular function. METHODS: Nematodes expressing lgg-1::RFP, hsp1::GFP, hsp4::GFP and hsp6::GFP were crossed to nematode lines expressing WT, GS, RC or kinase dead LRRK2. RESULTS: We observed that GS and RC LRRK2 inhibited autophagy, while WT, GS and RC LRRK2 increased the response of the mitochondrial hsp6 reporter to stress. The response of the hsp reporters under basal conditions was more nuanced. CONCLUSION: These results support a putative role of LRRK2 in the autophagic and mitochondrial systems.
Authors: Samer Matta; Kristof Van Kolen; Raquel da Cunha; Geert van den Bogaart; Wim Mandemakers; Katarzyna Miskiewicz; Pieter-Jan De Bock; Vanessa A Morais; Sven Vilain; Dominik Haddad; Lore Delbroek; Jef Swerts; Lucía Chávez-Gutiérrez; Giovanni Esposito; Guy Daneels; Eric Karran; Matthew Holt; Kris Gevaert; Diederik W Moechars; Bart De Strooper; Patrik Verstreken Journal: Neuron Date: 2012-09-20 Impact factor: 17.173
Authors: Youren Tong; Hiroo Yamaguchi; Emilie Giaime; Scott Boyle; Raphael Kopan; Raymond J Kelleher; Jie Shen Journal: Proc Natl Acad Sci U S A Date: 2010-05-10 Impact factor: 11.205
Authors: Hanna Kim; Carles Calatayud; Sanjib Guha; Irene Fernández-Carasa; Laura Berkowitz; Iria Carballo-Carbajal; Mario Ezquerra; Rubén Fernández-Santiago; Pankaj Kapahi; Ángel Raya; Antonio Miranda-Vizuete; Jose Miguel Lizcano; Miquel Vila; Kim A Caldwell; Guy A Caldwell; Antonella Consiglio; Esther Dalfo Journal: Mol Neurobiol Date: 2018-02-10 Impact factor: 5.590
Authors: Jason F Cooper; Dylan J Dues; Katie K Spielbauer; Emily Machiela; Megan M Senchuk; Jeremy M Van Raamsdonk Journal: NPJ Parkinsons Dis Date: 2015-11-19